RATIONALE: Drugs used in chemotherapy work in different ways to stop the growth of plasma cells, either by killing the cells or by stopping them from dividing. Having a peripheral stem cell transplant to replace the blood-forming cells destroyed by chemotherapy, allows higher dose of chemotherapy to be given so that more plasma cells are killed. Giving a chemoprotective drug such as amifostine may protect kidney cells from the side effects of chemotherapy.

PURPOSE: This phase I trial is studying the side effects and best dose of melphalan given together with amifostine in treating patients who are undergoing peripheral stem cell transplant for primary systemic amyloidosis.

Further study details as provided by Eastern Cooperative Oncology Group:

Primary Outcome Measures:

Maximum Tolerated Dose [ Time Frame: Assessed over 30 days ]

The maximum tolerated dose is the highest dose level at which fewer than 1 of 3 or 2 of 6 patients experience dose-limiting toxicity, defined as any grade 3 or higher toxicity of any of the following: renal failure, alkaline phosphatase elevation, GI bleeding, and cardiac rhythm disturbances, assessed using NCI Common Toxicity Criteria, version 2.0.

Determine the toxicity of high-dose melphalan when administered at the MTD in these patients.

Determine the response rate in patients treated with this regimen.

OUTLINE: This is a nonrandomized, multicenter, dose-escalation study of melphalan.

Patients receive filgrastim (G-CSF) subcutaneously once daily until peripheral blood stem cell (PBSC) collection is complete. Apheresis begins on day 5 of G-CSF administration and continues until the target number of PBSCs are collected.

Within 6 weeks of PBSC collection, patients receive amifostine IV over 5 minutes on days -2 and -1 and high-dose melphalan IV over 30-60 minutes on day -1. Patients undergo autologous PBSC infusion on day 0.

Cohorts of 3-6 patients receive escalating doses of melphalan until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Once the MTD is determined, an additional 10 patients are treated at that dose.

Patients are followed approximately 3 months following transplantation, then every 6 months for 5 years.

PROJECTED ACCRUAL: A total of 3-46 patients will be accrued for this study within 2.3 years.

Eligibility

Ages Eligible for Study:

18 Years to 70 Years (Adult, Senior)

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

No

Criteria

DISEASE CHARACTERISTICS:

Histologically confirmed amyloidosis

No secondary familial or localized amyloidosis

Presence of monoclonal protein by immunoelectrophoresis or immunofixation of serum or urine

No primary amyloidosis manifested only by carpal tunnel syndrome or purpura

Amyloid deposits in a plasmacytoma or in bone marrow vessels in an asymptomatic individual not considered an amyloid syndrome

Amyloid syndromes include any of the following:

Hepatomegaly

Cardiomyopathy

Nephrotic range proteinuria

Peripheral or autonomic neuropathy

No multiple myeloma defined by 1 of the following:

Presence of lytic bone disease

More than 30% bone marrow plasma cells

PATIENT CHARACTERISTICS:

Age

18 to 70

Performance status

ECOG 0-1

Life expectancy

Not specified

Hematopoietic

Platelet count at least 100,000/mm^3

Hepatic

See Disease Characteristics

Total or direct bilirubin no greater than 2.0 mg/dL

Alkaline phosphatase no greater than 4 times upper limit of normal

Renal

See Disease Characteristics

Creatinine less than 3.0 mg/dL

Cardiovascular

See Disease Characteristics

Ejection fraction at least 45% by echocardiogram

No New York Heart Association class III or IV heart disease

Systolic blood pressure ≥ 90 mmHg

Other

Not pregnant or nursing

Negative pregnancy test

Fertile patients must use effective contraception

No active infection

No other malignancy within the past 5 years except surgically treated carcinoma in situ of the cervix, nonmelanoma skin cancer, or indolent prostate cancer

PRIOR CONCURRENT THERAPY:

Biologic therapy

At least 4 weeks since prior interferon

Chemotherapy

At least 4 weeks since prior melphalan

Lifetime total melphalan dose less than 150 mg/m^2 (based on ideal body weight)

Endocrine therapy

At least 4 weeks since prior dexamethasone

Radiotherapy

No prior radiotherapy for amyloidosis

Surgery

Not specified

Other

No antihypertensive medications for at least 24 hours prior to, during, and for 1 hour after amifostine administration

No other prior treatment

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study.
To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00052884